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Pyridazinones containing the (4-methoxyphenyl)piperazine moiety as AChE/BChE inhibitors: design, synthesis, in silico and biological evaluationMerde, İrem B.Önel, Gülce T.Türkmenoğlu, BurçinGürsoy, ŞuleDilek, Esra1,2,4-triazole3(2H)-pyridazinoneAChE/BChE inhibitory activityAlzheimer’s diseaseMolecular docking(4 methoxyphenyl)piperazine derivative1,2,4 triazole derivative2 [[4 (4 bromophenyl) 5 thioxo 4,5 dihydro 1h 1,2,4 triazol 3 yl]methyl] 6 [4 (4 methoxyphenyl)piperazin 1 yl]pyridazin 3(2h) one2 [[4 (4 fluorophenyl) 5 thioxo 4,5 dihydro 1h 1,2,4 triazol 3 yl]methyl] 6 [4 (4 methoxyphenyl)piperazin 1 yl]pyridazin 3(2h) one6 [4 (4 methoxyphenyl)piperazin 1 yl] 2 [(4 phenyl 5 thioxo 4,5 dihydro 1h 1,2,4 triazol 3 yl)methyl]pyridazin 3(2h) one6 [4 (4 methoxyphenyl)piperazin 1 yl] 2 [(5 thioxo 4 (4 tolyl) 4,5 dihydro 1h 1,2,4 triazol 3 yl)methyl]pyridazin 3(2h) one6 [4 (4 methoxyphenyl)piperazin 1 yl] 2 [[5 thioxo 4 [4 (trifluoromethoxy)phenyl] 4,5 dihydro 1h 1,2,4 triazol 3 yl]methyl]pyridazin 3(2h) oneacetylcholinesteraseamino acidcholinesterasecholinesterase inhibitormethyl groupphenyl grouppiperazine derivativepyridazinone derivativetacrineunclassified drugAlzheimer diseaseArticlebinding affinitybinding sitebiological activitycompetitive inhibitioncomputer modelconcentration responseAlzheimer’s disease is a progressive and fatal neurodegenerative disease affecting the elderly population accompanied by a decrease in cholinergic transmission, impairing cognitive functions. Acetylcholine deficiency is important in the development of disease symptoms. Inhibition of acetylcholinesterase, an important enzyme in acetylcholine hydrolysis, is one of the important drug targets to increase acetylcholine levels. In this study, we aimed to develop acetylcholinesterase inhibitor compounds. For this, we synthesized compounds 6(a–e) bearing 3(2H)-pyridazinone and 1,2,4-triazole ring structures. We determined the IC50, Ki and inhibition types of N-substituted-(p-methoxyphenyl)pyridazin-3(2H)-one derivatives that we synthesized and elucidated their structures. The compound with the best AChE activity was compound 6b (Ki = 3.73 ± 0.9 nM) with the p-methylphenyl group it carried and showed competitive inhibition. Kinetic study was also performed for the compounds with the highest BChE 6a (Ki = 0.95 ± 0.16 nM) inhibitory activities. Molecular docking studies have shown that the p-methylphenyl group is indeed active in the hinge region of the AChE crystal structure as a result of experimental activity. In addition, the best free binding energy (ΔGBind), docking score and Glide score values were determined by examining the interactions with AChE crystal structure for compound 6b and with BChE crystal structure for 6a in silico approaches. [Figure not available: see fulltext.] © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Springer2022Articlehttps://rdlopen.rawdatalibrary.net/r/ebyu/12517https://doi.org/10.1007/s00044-022-02968-x1054-2523enMedicinal Chemistry Researchinfo:eu-repo/semantics/openAccessinfo:eu-repo/semantics/articlehttps://ebyu-rdlopen.rawdatalibrary.net/tr/items/ebyu/12517